Marine anti-malarial isonitriles : a synthetic and computational study

The development of Plasmodium falciparum malarial resistance to the current armoury of anti-malarial drugs requires the development of new treatments to help combat this disease. The marine environment is a well established source of potential pharmaceuticals. Of interest to us are isonitrile, isocyanate and isothiocyanate compounds isolated from marine sponges and molluscs which have exhibited nano-molar anti-plasmodial activities. Through quantitative structure-activity relation studies (QSAR), a literature precedent exists for a pseudoreceptor model from which a pharmacophore for the design of novel anti-malarial agents was proposed. The current theory suggests that these marine compounds exert their inhibitory action through interfering with the heme detoxification pathway in P. falciparum. We propose that the computational methods used to draw detailed conclusions about the mode of action of these marine compounds were inadequate. This thesis addresses this problem using contemporary computational methodologies and seeks to propose a more robust method for the rational design of new anti-malarial drug compounds that inhibit heme polymerization to hemozoin. In order to investigate the interactions of the marine compounds with their heme targets, a series of modern computational procedures were formulated, validated and then applied to theoretical systems. The validations of these algorithms, before their application to the marine compound-heme systems, were achieved through two case studies. The first was used to investigate the applicability of the statistical docking algorithm AutoDock to be used for the exploration of conformational space around the heme target. A theoretical P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) enzyme model, constructed by the Biochemistry Department at Rhodes University, provided the ideal model to validate the AutoDock program. The protein model was accordingly subjected to rigorous docking simulations with over 30 different ligand molecules using the AutoDock algorithm which allowed for the docking algorithm’s limitations to be ascertained and improved upon. This investigation facilitated the successful validation of the protein model, which can now be used for the rational design of new PfDXR-inhibiting anti-plasmodial compounds, as well as enabling us to propose an improvement of the docking algorithm for application to the heme systems. The second case study was used to investigate the applicability of an ab initio molecular dynamics algorithm for simulation of bond breaking/forming events between the marine compounds and their heme target. This validation involved the exploration of intermolecular interactions in a naturally occurring nonoligomeric zipper using the Car-Parrinello Molecular Dynamics (CPMD) method. This study allowed us to propose a model for the intermolecular forces responsible for zipper self-assembly and showcased the CPMD method’s abilities to simulate and predict bond forming/breaking events. Data from the computational analyses suggested that the interactions between marine isonitriles, isocyanates and isothiocyanates occur through bond-less electrostatic attractions rather than through formal intermolecular bonds as had been previously suggested. Accordingly, a simple bicyclic tertiary isonitrile (5.14) was synthesized using Kitano et al’s relatively underutilized isonitrile synthetic method for the conversion of tertiary alcohols to their corresponding isonitriles. This compound’s potential for heme detoxification inhibition was then explored in vitro via the pyridine-hemochrome assay. The assay data suggested that the synthesized isonitrile was capable of inhibiting heme polymerization in a similar fashion to the known inhibitor chloroquine. Attempts to synthesize tricyclic analogues of 5.14 were unsuccessful and highlighted the limitation of Kitano et al’s isonitrile synthetic methodology

Re-thinking engagement: Dialogic strategies of alignment in letters to two South African newspapers

This article uses an appraisal analysis of 40 letters to the Daily Sun and The Times newspapers in South Africa to illustrate a reconceptualisation of the Engagement system. It discusses dialogism (Bakhtin 1981), which inspired the creation of the Engagement framework by White (2003), who classified attempts to either align or disalign readers with a writer’s stance. Contrary to the options for dialogic Engagement proposed by Martin and White (2005) and White and Don (2012), the data suggests that not all Engagement strategies carry equal power of alignment, as the framework’s systemic layout implies. This prompts a re-thinking of the Engagement categories as occurring along a continuum of their strength

Newspaper literacy and communication for democracy: is there a crisis in South African journalism?

Media theorists such as Barnett (2002), Buckingham (1997 & 2000) and Sampson (1999) describe a perceived crisis hindering the media’s ability to inform citizens for participation in democracy. One of the symptoms and causes of this crisis, they argue, is that the media use language that many citizens cannot understand. This article draws on theories and methodologies from linguistics to investigate whether this claim holds true for South African newspapers. The concept of the crisis in journalism is deconstructed in the light of Street’s (1984) ideological model of literacy. In a pilot study, multiple readability tests were conducted on one article from each of three newspapers, Business Day, The Herald and Daily Sun. The findings of these tests, and a systemic functional grammar analysis of cohesion and lexical density in the three articles, show that all three newspapers tailor their language to fit their target markets. This, triangulated with the rapid growth in readership of the Daily Sun and the more modest growth of The Herald, suggests that many South Africans are better informed for participation in democracy than in the past, although newspapers can do more to help readers learn a plurality of literacy practices

An APPRAISAL analysis of the discourse of student assistants' reports at an Eastern Cape girls' boarding school

This article reports on a pilot investigation into the language of assessment in a bi-weekly report system of an urban South African all-girls boarding school. The data are drawn principally from four student assistants working in one of the school’s hostels and are analysed using the theoretical framework of APPRAISAL. The focus is on the APPRAISAL resources that the stooges use in writing their reports, specifically their choices from the ATTITUDE and GRADUATION subsystems. Analysis indicates that Judgement and Affect instantiations, augmented by the use of Force rather than Focus, are dominant. There is also individual variation within the overarching prosody, indicating a difference between the ‘newer’ and the ‘older’ student assistants’ reports. We argue that such choices reflect and reaffirm the school’s core values and vision, the reports functioning as monitors of behaviour and as a means of aligning the learners with the school’s standards. The matron’s feedback is suggested to be an added measure of ensuring alignment with the school’s values

Newspapers as ‘community members’: Editorial responses to the death of Eugene Terre'Blanche

This article uses the appraisal system to expose covert meanings surrounding white supremacist Eugène Terre’Blanche’s murder in editorials from three South African newspapers: The Citizen, Sowetan and The Times. Following Martin and White’s (2005) framework, inscribed and evoked Attitudinal meanings are identified to prove an ‘us versus them’ perspective of Terre’Blanche’s death. Graduation and Engagement strategies supplement this, illustrating how meanings are modified or organized to align readers. The analysis reveals surface attempts to present a ‘balanced view’ of this racially-sensitive event; however, beneath this is clear blame allocation. Additionally, the covert evaluation is explained by Coffin and O’Halloran’s (2006) theory of ‘dog-whistling’, where only aligned readers can detect underlying meanings. This creates the imagined community – ‘us’ – of which the newspaper is seen as a trusted member. Print media, it could be inferred, is symbolic of other South African community members, who mask their evaluations with a politically correct façade

Development of a translation device for axiological-semantic density in political news articles: Wording and charging

The concept of axiological-semantic density from Legitimation Code Theory (LCT) is extremely helpful in analysing political knowledge-building, as it describes the strength of relations between various people, political stances and moral judgements, enabling these to be positioned in relation to each other. We present a multi-level translation device designed to identify strengths of axiological-semantic density in political news articles from the Daily Sun, South Africa’s most popular tabloid newspaper. This translation device was devised through analysis of selected texts from a corpus of 516 articles published between January and June 2015. It was developed through a collaborative process involving the first author and a team of student research assistants. The final translation device has five tools, of which two, the wording and charging tools, are described in this article, and then illustrated using an example analysis of a Daily Sun political news article. Both tools reveal insights into South African political discourses and ways in which axiological-semantic density can be enacted in future research. Making axiological-semantic density visible using such a translation device also has practical applications in assisting readers to understand the ways in which publications such as the Daily Sun position political parties, enabling them to engage more constructively in discussions on the country’s future

“Eye on the big prize!”: Iconizing the Democratic Alliance in the Daily Sun

This article gives a snapshot view of how Mmusi Maimane’s rise to leadership in the Democratic Alliance (DA) in 2015 was reported on in the Daily Sun, South Africa’s biggest-selling national daily newspaper (South African Audience Research Foundation, 2016). Through analysis of a Daily Sun news article exemplifying trends in the positioning of the DA in the tabloid over the first half of 2015, the present study demonstrates how Maimane tried to align the DA around a new iconography (Tann 2010, 2013), centred on the values of “freedom”, “fairness” and “opportunity”. Moreover, the present study also shows how this purported transformation in the DA was treated with scepticism by the news article’s author, who iconizes the DA as incapable of transformation and effective governance. Fine-grained complementary Legitimation Code Theory (LCT) and Systemic Functional Linguistics (SFL) analyses were conducted on this news article. The LCT analysis shows how multiple voices in the news article create conflicting binary constellations, axiologically charged through various linguistic resources, including intertextual references. The analysis, using SFL’s Appraisal system (Martin and White 2005), shows how iconization is accomplished in the news article through evaluative language, coupled with intertextual references, grammatical metaphor andtechnicality to produce syndromes of meaning in the news article. Such iconization works, in this case, to reproduce an attitude of cynicism toward party politics in post-apartheid South Africa. This cynicism foreshadows Maimane’s ultimate lack of success in transforming the discourses of the DA

Constellations, technicality, iconisation and Eskom: A case from South Africa’s Business Day

This article uses Legitimation Code Theory (LCT) and systemic functional linguistics (SFL) to explore interactions between various resources for building economic and political knowledge in a 2015 article from Business Day, a South African newspaper, concerning the country’s energy crisis. We use LCT to observe how three constellations are built in the article: a ‘developmental state’ constellation; a ‘neo-liberal’ constellation; and another underarticulated constellation that selectively draws ideas from both the preceding constellations. These constellations are built through the unfolding of the text using various linguistic resources, which we describe using SFL, including technicality and iconisation. We identify instances where words are charged with both ideational and axiological meaning concurrently, challenging existing understandings of the process of iconisation

Comprehension and production of figurative language by Afrikaans-speaking children with and without specific language impairment

This article reports on the comprehension and production of figurative language, namely idioms and similes, in first language Afrikaans-speaking (AFR) boys, ages eight to 10 years, and first language Afrikaans-speaking boys with specific language impairment (SLI), also ages eight to 10. It draws on a larger study by Van der Merwe (2007; see also Van der Merwe & Southwood, 2008). Testing of the comprehension and production abilities of the children was conducted verbally and individually and elicited their understanding of 25 idioms and 25 similes. The idioms were first presented without context; if the child gave an incorrect interpretation, the idiom was placed in context. Raw scores show that the SLI group performed marginally more poorly than the AFR group, but there was no statistically significant difference between the comprehension of idioms by the two groups. The same can be said for the number of literal interpretations provided by the groups. Placing the idioms in context was beneficial to both groups. The simile completion task required the children to provide the last word of each simile. For both groups, the similes task proved to be easier than the idioms task but there was again no statistically significant difference found between the two groups. The results seem to imply that children at this developmental phase, aged eight to 10, whether language impaired or not, have not yet fully grasped figurative language as a concept and need explicit instructions on figurative language. The article ends with a reflection on the suitability of idioms and similes as particular categories of figurative language in studies of this nature

Informed Interdependence: A model for collaboration in fostering communicative competencies in a Commerce curriculum

The current orthodoxy among academics in higher education studies is that content and language learning should be integrated in order to facilitate communicative competencies in degrees seeking to prepare students for business and professions such as accounting, engineering and pharmacy. Content and Language Integrated Learning (CLIL) has been well-theorised and its goals are laudable; however, we contend that a one-size-fits-all solution of complete integration is not the most practicable or pedagogically-sound option in all contexts. Instead, we argue that establishing relationships of Informed Interdependence between content and language courses may offer greater benefits in specific contexts. This argument may appear counterintuitive, but we believe it has significant insights to add to the continuing dialogue around the use of CLIL. Accordingly, we describe a Professional Communication course at Rhodes University and then outline how we have responded to changes in our context through a process of engagement which led to a new course, namely, Professional Communication for Accountants, and recurriculation of the original Professional Communication course. In reporting on this process we foreground the importance of suitable boundary objects and discursive spaces around which interdisciplinary collaboration can occur. We provide staff and student reactions to a pilot project designed to test the curricular innovations made thus far, and conclude by reflecting on the efficacy of an Informed Interdependence model in our context